CRF Receptor GPCR Assays
Introduction of Corticotropin Releasing Factor (CRF)
CRF, a key regulator of behavior, physiology, endocrine, and responses during stress, is often closely relevant to stress-related affective disorders such as depression and anxiety. Furthermore, the CRF system plays an important role in gastrointestinal pathophysiology. The CRF system consists of different ligands that bind with different affinities to two CRF receptors: CRFR1 and CRFR2. Notably, scientists have discovered that CRF receptors play a critical role in regulating the progression of a variety of diseases, such as colonic inflammation and carcinogenesis.
Fig.1 The CRF family and its relation with CRF-BP. (Vandael, 2019)
Distribution of CRF Receptors
The two CRF receptors are widely distributed. CRFR1 and CRF2 are expressed in the brain, aortic endothelial cells, gastrointestinal tract, hepatocytes, pancreatic beta cells, mast cells, and myometrium. However, CRFR1 is widely distributed in stress-responsive brain regions, including the centrally extending amygdala, neocortex, thalamus, hippocampus, and cerebellum. CRHR2 predominates in peripheral tissues.
Types and Mechanisms of CRF Receptors
CRF binds these two receptors with different strengths. There is compelling evidence that CRF activation of CRFR1 signaling can initiate anxiety-like defense responses and is necessary for many contexts. Importantly, CRFR1 antagonists have emerged as promising anxiolytic and antidepressant therapeutic strategies. The main types and mechanisms of action of CRF receptors are summarized in the table below.
| Receptor | Gene | Mechanism | Agonists | Antagonists |
| CRF1 Receptor | CRHR1 |
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| CRF2 Receptor | CRHR2 |
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Assay List of CRF Receptors
Creative Biolabs can provide a range of assays of CRF receptors. You can choose the assay in the list or contact us for more information:
Published Data
| Paper Title | Activation Mechanism of Corticotrophin Releasing Factor Receptor Type 1 Elucidated Using Molecular Dynamics Simulations |
| Journal | ACS chemical neuroscience |
| Published | 2021 |
| Abstract | CRHR1 is an attractive drug target for the treatment of anxiety, depression, and other stress-related neurological disorders. However, currently, drugs targeting CRHR1 are still in development. Fully understanding the structural information and activation mechanism of CRHR1 may facilitate the development of drugs targeting CRHR1. This article uses the crystal structures of the transmembrane domain and N-terminal extracellular domain of CRHR1 as templates to establish a full-length homology model of CRHR1 and its interaction with the peptide agonist urocortin 1 or small molecules complex. All-atom molecular dynamics simulations were performed for the antagonist CP-376395. The observed large-scale conformational changes involving activation of CRHR1 by agonist binding provide new insights into ligand design. |
| Result |
To explore the mechanism of CRHR1 activation, molecular dynamics simulations were performed for CRHR1 bound by agonist urocortin 1 and CRHR1 bound by antagonist CP-376395. The findings indicated a potential role for peptide agonists to stabilize transmembrane helices, but caused changes in their helical packing arrangement. This rearrangement may be associated with the breaking of salt bridges and hydrogen bonds between helices/regions. Furthermore, residues identified from simulations and dynamic network analysis overlapped with experimental mutagenesis data. The findings of this work have contributed to the design of ligands targeting CRHR1 for the treatment of stress-related diseases.
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Fig.2 Proposed mechanism of urocortin 1-induced CRHR1 activation. (Uba, 2021)
References
- Vandael, D.; Gounko, N. V. Corticotropin releasing factor-binding protein (CRF-BP) as a potential new therapeutic target in Alzheimer’s disease and stress disorders. Translational Psychiatry. 2019; 9(1): 1-11.
- Uba, A.I.; et al. Gounko, N. V. Activation Mechanism of Corticotrophin Releasing Factor Receptor Type 1 Elucidated Using Molecular Dynamics Simulations. ACS chemical neuroscience. 2021; 12(9): 1674-1687.
